E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/refractory acute leukaemia |
LEUCEMIA AGUDA EN RECAÍDA O REFRACTARIEDAD |
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E.1.1.1 | Medical condition in easily understood language |
Relapsed/refractory paediatric acute leukaemia |
LEUCEMIA AGUDA EN RECAÍDA O REFRACTARIEDAD |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000831 |
E.1.2 | Term | Acute leukaemia NOS |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety of mature peripheral blood haploidentical expanded and activated IL-15 stimulated NK cells (NKAE) immunotherapy after salvage chemotherapy in patients with relapsed or refractary acute leukemia |
Determinar la seguridad de la inmunoterapia con células NK diferenciadas adultas alogénicas haploidénticas de sangre periférica expandidas y activadas con IL-15 (NKAE) tras quimioterapia de rescate en pacientes con leucemia aguda en recaída o refractariedad. |
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E.2.2 | Secondary objectives of the trial |
Analyze incidence of episodes of febrile neutropenia, bacteremia, infections (viral and fungal), hematological recovery and days of hospitalization.
Evaluate complete remission rate (cytomorphological and by criteria of "minimal residual disease", flow cytometry and/or molecular biology) .
Assess immune reconstitution of lymphocytes and cytotoxic activity of NK cells pre and post NKAES infusion. |
Analizar la incidencia de episodios de neutropenia febril, bacteriemias, infecciones (víricas, fúngicas), recuperación hematológica e ingreso hospitalario.
Evaluar la tasa de remisión completa (citomorfológica y por criterios de "enfermedad mínima residual", citometría de flujo y/o biología molecular).
Evaluar la reconstitución inmune de poblaciones linfocitarias y la actividad citotóxica de las células NK pre y post infusión de NKAE. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients betweem 0 and 23 years of age with diagnosis of acute lymphoblastic leukemia, in second relapse situation, postransplant relapse or refractary, or
2. Patients betweem 0 and 23 years of age with diagnosis of acute myeloblastic leukemia, relapsed or refractary. (Patient must meet inclusion critaria 1 or 2)
3. Lansky index > 60%
4. Mild (<2) functional organs alteration (hepatic, renal, respiratory)
according to National Cancer Institute criteria (NCI CTCAE v4).
5. Left ventricular ejection fraction > 39%
6. To grant informed consent in accordance with the current legal
regulations.
7. Presence of a compatible haploidentical donor (father or mother or brother). |
1. Pacientes de edad comprendida entre 0 y 23 años diagnosticados de leucemia aguda linfoblástica en situación clínica de segunda recaída, de recaída postrasplante o en situación de refractariedad, o
2. Pacientes de edad comprendida entre 0 y 23 años diagnosticados de leucemia aguda mieloblástica en situación clínica de recaída o de refractariedad. (El paciente debe cumplir el criterio 1 o el criterio 2).
3. Índice de Lansky > 60%.
4. Alteración funcional de órganos (hepática, renal, respiratorio) leve
(<2), según los criterios del National Cancer Institute (NCI CTCAE v4).
5. Fracción de eyección del ventrículo izquierdo >39%.
6. Otorgar consentimiento informado de acuerdo con la normativa legal
vigente.
7. Presencia de un donante haploidéntico compatible (padre o madre o hermano). |
|
E.4 | Principal exclusion criteria |
1. Patients with a history of poor treatment compliance.
2. Patients following a psycho-social assessment are censored as unfit for the procedure.
3. Functional impairment of organs (liver, kidney, respiratory) severe (4), according to the criteria of the National Cancer Institute (NCI CTCAE 4.3).
4. Positive HIV serology.
5. Should be considered contraindications, interactions, precautions for use and dose reductions indicated in the respective data sheets. |
1. Pacientes con antecedentes de mal cumplimiento terapéutico.
2. Pacientes que tras una evaluación psico-social se censuran como no aptos para el procedimiento.
3. Alteración funcional de órganos (hepática, renal, respiratorio) grave (4), según los criterios del National Cáncer Institute (NCI CTCAE 4.3).
4. Serología HIV positiva.
5. Se deben considerar las contraindicaciones, interacciones, precauciones de uso y reducciones de dosis indicadas en las fichas técnicas correspondientes. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety of mature peripheral blood haploidentical expanded and activated IL-15 stimulated NK cells infusion after chemotherapy |
Seguridad de la infusión de células NK diferenciadas adultas alogénicas haploidénticas de sangre periférica expandidas y activadas con IL-15 tras quimioterapia. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2 months after infusion |
2 meses tras la infusión |
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E.5.2 | Secondary end point(s) |
1. Incidence of episodes of febrile neutropenia, bacteriemia or viral or fungal infections
2. Days of hematological recovery (neutrophils >500/microL, lymphocytes >250/microL and platelets >50.000/microL), days of hospitalization, in each cycle
3. Immune reconstitution: Median of T-cell , B, NK, NKT and dendritic cells count and subpopulations of T and NK lymphocytes (cel/microL) during post-treatment follow-up period
4. In vitro cytotoxic activity of NK cells of the patient measured by real-time fluorescence-TDA Eur compared with that of the donor (Blomberg et al. J Immunol Methods 1986)
5. Objective response rate according to cytomorphologic and by "minimal residual disease" criteria (cytometry and/or real time PCR) at the end of the treatment
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1. Incidencia de episodios de neutropenia febril, bacteriemia o infecciones víricas o fúngicas.
2. Días hasta recuperación hematológica (neutrófilos >500/microL, linfocitos >250/microL y plaquetas >50.000/microL, días de ingreso hospitalario, en cada ciclo.
3. Reconstitución inmune: Mediana de recuento de células T, B, NK, NKT, dendríticas y subpoblaciones de linfocitos T y NK (cel/microL) durante el periodo de seguimiento post-tratamiento.
4. Actividad citotóxica in vitro de las células NK del paciente comparándola con su donante medida con fluorescencia a tiempo real Eur-TDA (Blomberg et al. J Immunol Methods 1986)
5. Tasa de respuesta objetiva según los criterios citomorfológicos y por enfermedad mínima residual (citometría y/o PCR tiempo real) al final del tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. after each cycle
2. after each cycle
3. weekly
4. weekly
5. after treatment |
1. después de cada ciclo
2. después de cada ciclo
3. cada semana
4. cada semana
5. después del tratamiento
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of follow-up |
Final de seguimiento |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |